This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to explore specific interactions between smoked cocaine and exogenously administered progesterone. One hypothesis is that exogenous progesterone, adminstered during the follicular phase in women will reduce subjective responses to cocaine as well as cocaine self-administration. Progesterone or placebo treatment will be given during their menses when plasma estradiol and progesterone concentrations are normally low. This early follicular phase of the menstrual cycle provides an opportunity to investigate the effects of exogenously administered progesterone while minimizing the potential confounding influence of endogenous estradiol and progesterone. The hypothesis for men is that progesterone will attenuate the desire for and use of cocaine. A specific aim of the study will be to characterize the dose-related effects of progesterone on the physiological, subjective and reinforcing effects of smoked cocaine in a laboratory model. Healthy cocaine dependent female subjects will be admitted to the GCRC early in their menses (during two consecutive menstrual cycles) and begin oral progesterone, given BID. Male subjects will be admitted to the GCRC at the same time two consecutive months and receive dosing as per the females. All subjects will undergo an adaption phase where they will be introduced to the protocol and a dose of cocaine. During the experimental sessions on 2 consecutive days (3 &4) they will be given a sample dose of smoked cocaine and have the option to earn 5 tokens from doing a computer math test. They may then exchange these tokens (up to 5) for money (5.00) or a dose of smoked cocaine. Physiologic parameters will be monitored and GCRC nursing personnel will establish IV's and draw blood during the experiment. A physician will be in attendance. This study will allow dose-effects of progesterone to be studied. The doses of cocaine used are the same as in previous studies on the GCRC.